A facile and environmentally friendly Nafion-H catalyzed multicomponent reaction for synthesis of octahydroquinazolinone derivatives is described. In order to improve the yield and selectivity, the effects of the mole proportion of reactants (cyclic beta-diketones, urea and aldehydes) and solvents were investigated. The ability to reuse the catalyst, high yields and easy purification are important features of this process. Interestingly, under similar conditions, the use of nicotinaldehyde and isonicotinaldehyde as the aldehyde component of the reaction gives unexpected products that are distinct from Biginelli products. All of the products were characterized by H-1 NMR, C-13 NMR, EI-MS and IR, and the structure of one Biglnelli product (4k) was determined by single-crystal X-ray diffraction. (c) 2006 Elsevier B.V. All rights reserved.